JP6480944B2 - ブロモドメイン阻害剤としての二環式複素環誘導体 - Google Patents
ブロモドメイン阻害剤としての二環式複素環誘導体 Download PDFInfo
- Publication number
- JP6480944B2 JP6480944B2 JP2016545312A JP2016545312A JP6480944B2 JP 6480944 B2 JP6480944 B2 JP 6480944B2 JP 2016545312 A JP2016545312 A JP 2016545312A JP 2016545312 A JP2016545312 A JP 2016545312A JP 6480944 B2 JP6480944 B2 JP 6480944B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- dimethylisoxazol
- methoxy
- pyridin
- ylmethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102000001805 Bromodomains Human genes 0.000 title claims description 33
- 108050009021 Bromodomains Proteins 0.000 title claims description 30
- 239000003112 inhibitor Substances 0.000 title description 15
- 125000002618 bicyclic heterocycle group Chemical group 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims description 213
- -1 1- (4-chlorophenyl) ethyl Chemical group 0.000 claims description 116
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 125000001188 haloalkyl group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
- 229940125763 bromodomain inhibitor Drugs 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 108090000623 proteins and genes Proteins 0.000 claims description 10
- 125000002619 bicyclic group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 8
- 229940126657 Compound 17 Drugs 0.000 claims description 8
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 229940124530 sulfonamide Drugs 0.000 claims description 5
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 claims description 4
- LXJALZKCPQXVIU-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(trifluoromethoxy)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC(F)(F)F)CC1=NC=CC=C1)=O)C LXJALZKCPQXVIU-UHFFFAOYSA-N 0.000 claims description 4
- NSXYBKLKNINDDK-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-3-(hydroxymethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=C(C(N(C2=CC1OC)CC1=NC=CC=C1)=O)CO)C NSXYBKLKNINDDK-UHFFFAOYSA-N 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- VUEGYUOUAAVYAS-JGGQBBKZSA-N (6ar,9s,10ar)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CNC3=C1 VUEGYUOUAAVYAS-JGGQBBKZSA-N 0.000 claims description 3
- LZSLAAORXALGHX-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxyquinoxalin-2-one Chemical compound COC1=CC2=C(C=C1C1=C(C)ON=C1C)N=CC(=O)N2CC1=CC=C(Cl)C=C1 LZSLAAORXALGHX-UHFFFAOYSA-N 0.000 claims description 3
- GAUJOEUMVMWRHY-UHFFFAOYSA-N 1-[(5-bromopyridin-2-yl)methyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxyquinolin-2-one Chemical compound COC1=CC2=C(C=CC(=O)N2CC2=NC=C(Br)C=C2)C=C1C1=C(C)ON=C1C GAUJOEUMVMWRHY-UHFFFAOYSA-N 0.000 claims description 3
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 claims description 3
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 3
- MYUKUIKWOQHVEV-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-3-(fluoromethyl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=C(C(N(C2=CC1OC)CC1=NC=CC=C1)=O)CF)C MYUKUIKWOQHVEV-UHFFFAOYSA-N 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 229940125904 compound 1 Drugs 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 2
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 claims description 2
- NZSBVAWTNWLABL-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3,4-dihydroquinolin-2-one Chemical compound ClC1=CC=C(CN2C(CCC3=CC(=C(C=C23)OC)C=2C(=NOC=2C)C)=O)C=C1 NZSBVAWTNWLABL-UHFFFAOYSA-N 0.000 claims description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 claims description 2
- FICAQKBMCKEFDI-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole Chemical compound CC=1C=C(C)ON=1 FICAQKBMCKEFDI-UHFFFAOYSA-N 0.000 claims description 2
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 claims description 2
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 claims description 2
- MZQKAAFGKZDPDH-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(2-piperazin-1-ylethoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC=1OCCN1CCNCC1)CC1=NC=CC=C1)=O)C MZQKAAFGKZDPDH-UHFFFAOYSA-N 0.000 claims description 2
- FXNMVZTWYPWSDU-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinoxalin-2-one Chemical compound CC1=NOC(=C1C=1C=C2N=CC(N(C2=CC1OC)CC1=NC=CC=C1)=O)C FXNMVZTWYPWSDU-UHFFFAOYSA-N 0.000 claims description 2
- NYUQSBMYDSDDRN-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-[[5-(1-methylpyrazol-4-yl)pyridin-2-yl]methyl]quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC=1OC)CC1=NC=C(C=C1)C=1C=NN(C=1)C)=O)C NYUQSBMYDSDDRN-UHFFFAOYSA-N 0.000 claims description 2
- LWUVSSBVBXVHFB-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(piperidin-4-ylmethyl)-1,4-benzoxazin-3-one Chemical compound COC1=CC2=C(OCC(=O)N2CC2CCNCC2)C=C1C1=C(C)ON=C1C LWUVSSBVBXVHFB-UHFFFAOYSA-N 0.000 claims description 2
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 claims description 2
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 229940125773 compound 10 Drugs 0.000 claims description 2
- 229940126142 compound 16 Drugs 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims description 2
- 229940126179 compound 72 Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- KORFDBDOHJBIRP-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1-hydroxyethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=C(C(N(C2=CC1OC)CC1=NC=CC=C1)=O)C(C(F)(F)F)O)C KORFDBDOHJBIRP-UHFFFAOYSA-N 0.000 claims 3
- XWXWBZCBJCMSGC-UHFFFAOYSA-N 4-[1-(4-chlorophenyl)ethyl]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-1,4-benzoxazin-3-one Chemical compound ClC1=CC=C(C=C1)C(C)N1C2=C(OCC1=O)C=C(C(=C2)OC)C=2C(=NOC2C)C XWXWBZCBJCMSGC-UHFFFAOYSA-N 0.000 claims 2
- YBJCCDDVKXUJJE-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(1-pyridin-3-ylethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2C(C)C=2C=NC=CC2)=O)C1)OC)C YBJCCDDVKXUJJE-UHFFFAOYSA-N 0.000 claims 2
- WOJQPBOZLCCBMO-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(1-pyridin-4-ylethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2C(C)C2=CC=NC=C2)=O)C1)OC)C WOJQPBOZLCCBMO-UHFFFAOYSA-N 0.000 claims 2
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 claims 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims 1
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 claims 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 claims 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims 1
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 claims 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 claims 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims 1
- OMBVEVHRIQULKW-DNQXCXABSA-M (3r,5r)-7-[3-(4-fluorophenyl)-8-oxo-7-phenyl-1-propan-2-yl-5,6-dihydro-4h-pyrrolo[2,3-c]azepin-2-yl]-3,5-dihydroxyheptanoate Chemical compound O=C1C=2N(C(C)C)C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C=3C=CC(F)=CC=3)C=2CCCN1C1=CC=CC=C1 OMBVEVHRIQULKW-DNQXCXABSA-M 0.000 claims 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 claims 1
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 claims 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 claims 1
- BYSXUMOVXBEFSO-UHFFFAOYSA-N 1-(4-chlorobenzoyl)-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxyquinolin-2-one Chemical compound COC1=CC2=C(C=CC(=O)N2C(=O)C2=CC=C(Cl)C=C2)C=C1C1=C(C)ON=C1C BYSXUMOVXBEFSO-UHFFFAOYSA-N 0.000 claims 1
- UXXHFEIITSJDSZ-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxyquinolin-2-one Chemical compound COC1=CC2=C(C=CC(=O)N2S(=O)(=O)C2=CC=C(Cl)C=C2)C=C1C1=C(C)ON=C1C UXXHFEIITSJDSZ-UHFFFAOYSA-N 0.000 claims 1
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 claims 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 claims 1
- HCKXDBNROSNPBE-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxyquinolin-2-one Chemical compound COC1=CC2=C(C=CC(=O)N2CC2=CC=C(Cl)C=C2)C=C1C1=C(C)ON=C1C HCKXDBNROSNPBE-UHFFFAOYSA-N 0.000 claims 1
- JPTAQSUNBYXXOW-UHFFFAOYSA-N 1-[(5-chloropyridin-2-yl)methyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-hydroxyquinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=CC2=C(C=C1O)N(CC1=NC=C(Cl)C=C1)C(=O)C=C2 JPTAQSUNBYXXOW-UHFFFAOYSA-N 0.000 claims 1
- DFTHZPMNZVGHFM-UHFFFAOYSA-N 1-[(5-chloropyridin-2-yl)methyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3-methylquinolin-2-one Chemical compound COC1=C(C=C2C=C(C)C(=O)N(CC3=NC=C(Cl)C=C3)C2=C1)C1=C(C)ON=C1C DFTHZPMNZVGHFM-UHFFFAOYSA-N 0.000 claims 1
- OKVJHDWHLOJXTR-UHFFFAOYSA-N 1-[(5-chloropyridin-2-yl)methyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxyquinolin-2-one Chemical compound COC1=C(C=C2C=CC(=O)N(CC3=NC=C(Cl)C=C3)C2=C1)C1=C(C)ON=C1C OKVJHDWHLOJXTR-UHFFFAOYSA-N 0.000 claims 1
- SCEWWDBTWYNYHY-UHFFFAOYSA-N 1-[(6-chloropyridin-3-yl)methyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxyquinolin-2-one Chemical compound COC1=C(C=C2C=CC(=O)N(CC3=CN=C(Cl)C=C3)C2=C1)C1=C(C)ON=C1C SCEWWDBTWYNYHY-UHFFFAOYSA-N 0.000 claims 1
- ASWDVHYLTREYJE-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3-methylquinolin-2-one Chemical compound COC1=C(C=C2C=C(C)C(=O)N(CCC3=CC=C(Cl)C=C3)C2=C1)C1=C(C)ON=C1C ASWDVHYLTREYJE-UHFFFAOYSA-N 0.000 claims 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims 1
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 claims 1
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 claims 1
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 claims 1
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 claims 1
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 claims 1
- LKPUVVZLGOGWOZ-UHFFFAOYSA-N 2-[[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2,3-dihydro-1,4-benzoxazin-4-yl]methyl]aniline Chemical compound COC1=CC2=C(OCCN2CC2=C(N)C=CC=C2)C=C1C1=C(C)ON=C1C LKPUVVZLGOGWOZ-UHFFFAOYSA-N 0.000 claims 1
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 claims 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 claims 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 claims 1
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 claims 1
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 claims 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 claims 1
- SRAXNVFAMZBEBS-UHFFFAOYSA-N 3-[7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)quinolin-6-yl]-4-methylpyrrole-2,5-dione Chemical compound COC1=CC2=C(C=CC(=O)N2CC2=NC=CC=C2)C=C1C1=C(C)C(=O)NC1=O SRAXNVFAMZBEBS-UHFFFAOYSA-N 0.000 claims 1
- PYOIYVGUPRUWBY-UHFFFAOYSA-N 3-cyclohexyl-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=C(C3CCCCC3)C(=O)N(CC3=NC=CC=C3)C2=C1)C1=C(C)ON=C1C PYOIYVGUPRUWBY-UHFFFAOYSA-N 0.000 claims 1
- CZGFZOISWNSMHZ-UHFFFAOYSA-N 3-cyclohexyl-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-3-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=C(C3CCCCC3)C(=O)N(CC3=CN=CC=C3)C2=C1)C1=C(C)ON=C1C CZGFZOISWNSMHZ-UHFFFAOYSA-N 0.000 claims 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 1
- GVBVZYGFAUKWBM-UHFFFAOYSA-N 4-(3-chlorophenyl)sulfonyl-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2,3-dihydro-1,4-benzoxazine Chemical compound ClC=1C=C(C=CC1)S(=O)(=O)N1C2=C(OCC1)C=C(C(=C2)OC)C=2C(=NOC2C)C GVBVZYGFAUKWBM-UHFFFAOYSA-N 0.000 claims 1
- HWXAMGTWUJTUNN-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-1,4-benzoxazin-3-one Chemical compound ClC1=CC=C(CN2C3=C(OCC2=O)C=C(C(=C3)OC)C=3C(=NOC3C)C)C=C1 HWXAMGTWUJTUNN-UHFFFAOYSA-N 0.000 claims 1
- QYWOLKVTQWOHRO-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2,3-dihydro-1,4-benzoxazine Chemical compound ClC1=CC=C(CN2C3=C(OCC2)C=C(C(=C3)OC)C=2C(=NOC=2C)C)C=C1 QYWOLKVTQWOHRO-UHFFFAOYSA-N 0.000 claims 1
- UYTWVGACHGTRMS-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-7-(3,5-dimethyl-1H-pyrazol-4-yl)-6-methoxy-1,4-benzoxazin-3-one Chemical compound COC1=C(C=C2OCC(=O)N(CC3=CC=C(Cl)C=C3)C2=C1)C1=C(C)NN=C1C UYTWVGACHGTRMS-UHFFFAOYSA-N 0.000 claims 1
- MAODLMJDXCCUAS-UHFFFAOYSA-N 4-[(5-chloropyridin-2-yl)methyl]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-1,4-benzoxazin-3-one Chemical compound ClC=1C=CC(=NC1)CN1C2=C(OCC1=O)C=C(C(=C2)OC)C=2C(=NOC2C)C MAODLMJDXCCUAS-UHFFFAOYSA-N 0.000 claims 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 claims 1
- XITXXHLWJQJXKF-UHFFFAOYSA-N 4-cyclopropyl-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C(=CC(=O)N(CC3=NC=CC=C3)C2=C1)C1CC1)C1=C(C)ON=C1C XITXXHLWJQJXKF-UHFFFAOYSA-N 0.000 claims 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 claims 1
- MLQHQINZKCDHST-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2,4-triazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=CC(=O)N(CC3=NC=CC=C3)C2=C1)N1C(C)=NN=C1C MLQHQINZKCDHST-UHFFFAOYSA-N 0.000 claims 1
- QWHGJLDTLAGCNH-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(2,2,2-trifluoroethoxy)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(OCC(F)(F)F)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 QWHGJLDTLAGCNH-UHFFFAOYSA-N 0.000 claims 1
- XBYHJLCRRMNGBC-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(2-pyrrolidin-1-ylethoxy)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(OCCN2CCCC2)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 XBYHJLCRRMNGBC-UHFFFAOYSA-N 0.000 claims 1
- VIXRXOAGVCUAQA-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)-7-(2-pyrrolidin-3-ylethoxy)quinolin-2-one hydrochloride Chemical compound Cl.Cc1noc(C)c1-c1cc2ccc(=O)n(Cc3ccccn3)c2cc1OCCC1CCNC1 VIXRXOAGVCUAQA-UHFFFAOYSA-N 0.000 claims 1
- KIRYATQAFAMXRG-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3-fluoropyridin-2-yl)methyl]-7-methoxyquinolin-2-one Chemical compound COC1=C(C=C2C=CC(=O)N(CC3=NC=CC=C3F)C2=C1)C1=C(C)ON=C1C KIRYATQAFAMXRG-UHFFFAOYSA-N 0.000 claims 1
- VPTNNSOPNCOHQZ-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(5-fluoropyridin-2-yl)methyl]-7-methoxyquinolin-2-one Chemical compound COC1=C(C=C2C=CC(=O)N(CC3=NC=C(F)C=C3)C2=C1)C1=C(C)ON=C1C VPTNNSOPNCOHQZ-UHFFFAOYSA-N 0.000 claims 1
- SHVRLTFEMRFZEX-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[[5-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-2-yl]methyl]-7-methoxyquinolin-2-one Chemical compound CC1=NNC(=C1C=1C=CC(=NC=1)CN1C(C=CC2=CC(=C(C=C12)OC)C=1C(=NOC=1C)C)=O)C SHVRLTFEMRFZEX-UHFFFAOYSA-N 0.000 claims 1
- SHZKPBLWFXRUTL-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[[5-(3-hydroxypyrrolidin-1-yl)pyridin-2-yl]methyl]-7-methoxyquinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC=1OC)CC1=NC=C(C=C1)N1CC(CC1)O)=O)C SHZKPBLWFXRUTL-UHFFFAOYSA-N 0.000 claims 1
- OAVYHERNZVHDFP-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(2-hydroxyethoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(OCCO)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 OAVYHERNZVHDFP-UHFFFAOYSA-N 0.000 claims 1
- RINBISSAHMWINJ-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(2-morpholin-4-ylethoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(OCCN2CCOCC2)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 RINBISSAHMWINJ-UHFFFAOYSA-N 0.000 claims 1
- JMMFLKGFUBNAKA-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(2-piperidin-4-ylethoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC=1OCCC1CCNCC1)CC1=NC=CC=C1)=O)C JMMFLKGFUBNAKA-UHFFFAOYSA-N 0.000 claims 1
- OCNSZVQUZYVHSE-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(3-hydroxypropoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(OCCCO)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 OCNSZVQUZYVHSE-UHFFFAOYSA-N 0.000 claims 1
- UOPIZDDCNDEIAM-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(oxan-4-ylmethoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(OCC2CCOCC2)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 UOPIZDDCNDEIAM-UHFFFAOYSA-N 0.000 claims 1
- MSECAQWKZQGRFJ-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(piperidin-4-ylmethoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(OCC2CCNCC2)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 MSECAQWKZQGRFJ-UHFFFAOYSA-N 0.000 claims 1
- LRQMTAYPCJYDQT-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(pyridin-4-ylmethoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(OCC2=CC=NC=C2)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 LRQMTAYPCJYDQT-UHFFFAOYSA-N 0.000 claims 1
- UZFVAOBKSOQXCJ-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-hydroxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=C(C(C)=NO1)C1=C(O)C=C2N(CC3=NC=CC=C3)C(=O)C=CC2=C1 UZFVAOBKSOQXCJ-UHFFFAOYSA-N 0.000 claims 1
- KVKFLBAIIXXMDH-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(1,3-thiazol-2-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)CC=1SC=CN1)=O)C KVKFLBAIIXXMDH-UHFFFAOYSA-N 0.000 claims 1
- XNFRSTCUEPVOBO-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(1-pyridin-2-ylethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)C(C)C1=NC=CC=C1)=O)C XNFRSTCUEPVOBO-UHFFFAOYSA-N 0.000 claims 1
- DYJTXQBJIGKDGV-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(1-pyridin-3-ylethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)C(C)C=1C=NC=CC1)=O)C DYJTXQBJIGKDGV-UHFFFAOYSA-N 0.000 claims 1
- YDAQUIURWGQOBG-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(2-morpholin-4-ylethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)CCN1CCOCC1)=O)C YDAQUIURWGQOBG-UHFFFAOYSA-N 0.000 claims 1
- SMYWLFUTIVCYAF-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(2-pyridin-2-ylethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)CCC1=NC=CC=C1)=O)C SMYWLFUTIVCYAF-UHFFFAOYSA-N 0.000 claims 1
- VRZGBLNSMAOTJH-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyrazin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=CC(=O)N(CC3=NC=CN=C3)C2=C1)C1=C(C)ON=C1C VRZGBLNSMAOTJH-UHFFFAOYSA-N 0.000 claims 1
- OIPIFASVOSSJHK-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3,4-dihydroquinolin-2-one Chemical compound COC1=C(C=C2CCC(=O)N(CC3=NC=CC=C3)C2=C1)C1=C(C)ON=C1C OIPIFASVOSSJHK-UHFFFAOYSA-N 0.000 claims 1
- CKUYRCCSVXHUOC-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-3-(2,2,2-trifluoro-1,1-dihydroxyethyl)quinolin-2-one Chemical compound COC1=CC2=C(C=C1C1=C(C)ON=C1C)C=C(C(=O)N2CC1=NC=CC=C1)C(O)(O)C(F)(F)F CKUYRCCSVXHUOC-UHFFFAOYSA-N 0.000 claims 1
- POGQAXXNQSUIBZ-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)-4-(trifluoromethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C(=CC(N(C2=CC1OC)CC1=NC=CC=C1)=O)C(F)(F)F)C POGQAXXNQSUIBZ-UHFFFAOYSA-N 0.000 claims 1
- PTHHHBOKUUKKCL-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)CC1=NC=CC=C1)=O)C PTHHHBOKUUKKCL-UHFFFAOYSA-N 0.000 claims 1
- GXHDROQIWLTJKM-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-3-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)CC=1C=NC=CC1)=O)C GXHDROQIWLTJKM-UHFFFAOYSA-N 0.000 claims 1
- NWOCKSNGLNHMMB-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyrimidin-2-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)CC1=NC=CC=N1)=O)C NWOCKSNGLNHMMB-UHFFFAOYSA-N 0.000 claims 1
- OKEWYPCIHLYQAH-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyrimidin-4-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)CC1=NC=NC=C1)=O)C OKEWYPCIHLYQAH-UHFFFAOYSA-N 0.000 claims 1
- VXXDEDWCGBCILC-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-(quinolin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=CC(=O)N(CC3=NC4=C(C=CC=C4)C=C3)C2=C1)C1=C(C)ON=C1C VXXDEDWCGBCILC-UHFFFAOYSA-N 0.000 claims 1
- PMMJUUSWEOKAQJ-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-[(5-methoxypyridin-2-yl)methyl]quinolin-2-one Chemical compound COC1=CN=C(CN2C(=O)C=CC3=CC(C4=C(C)ON=C4C)=C(OC)C=C23)C=C1 PMMJUUSWEOKAQJ-UHFFFAOYSA-N 0.000 claims 1
- PJPGHCWTFMIYNV-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1-[[5-(trifluoromethyl)pyridin-2-yl]methyl]quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC1OC)CC1=NC=C(C=C1)C(F)(F)F)=O)C PJPGHCWTFMIYNV-UHFFFAOYSA-N 0.000 claims 1
- WEDXMVNSVVPHTD-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3,3-dimethyl-1-(pyridin-2-ylmethyl)-4H-quinolin-2-one Chemical compound COC1=C(C=C2CC(C)(C)C(=O)N(CC3=NC=CC=C3)C2=C1)C1=C(C)ON=C1C WEDXMVNSVVPHTD-UHFFFAOYSA-N 0.000 claims 1
- IAFTUGHEISPLJU-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3,3-dimethyl-1-(pyridin-2-ylmethyl)quinoline-2,4-dione Chemical compound COC1=CC2=C(C=C1C1=C(C)ON=C1C)C(=O)C(C)(C)C(=O)N2CC1=NC=CC=C1 IAFTUGHEISPLJU-UHFFFAOYSA-N 0.000 claims 1
- YVGWSVHZXWFLIT-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3-methyl-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=C(C)C(=O)N(CC3=NC=CC=C3)C2=C1)C1=C(C)ON=C1C YVGWSVHZXWFLIT-UHFFFAOYSA-N 0.000 claims 1
- QDBBNYPSXUHFNP-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-4,4-dimethyl-1-(pyridin-2-ylmethyl)-3H-quinolin-2-one Chemical compound COC1=C(C=C2C(=C1)N(CC1=NC=CC=C1)C(=O)CC2(C)C)C1=C(C)ON=C1C QDBBNYPSXUHFNP-UHFFFAOYSA-N 0.000 claims 1
- PPNXHCHVPMYZRC-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-4-methyl-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C(C)=CC(=O)N(CC3=NC=CC=C3)C2=C1)C1=C(C)ON=C1C PPNXHCHVPMYZRC-UHFFFAOYSA-N 0.000 claims 1
- DPUPISKTXKGYQU-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-piperidin-4-yloxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(N(C2=CC=1OC1CCNCC1)CC1=NC=CC=C1)=O)C DPUPISKTXKGYQU-UHFFFAOYSA-N 0.000 claims 1
- QSUNKZHBZDXQPH-UHFFFAOYSA-N 6-(3,5-dimethyl-1H-pyrazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=CC(=O)N(CC3=NC=CC=C3)C2=C1)C1=C(C)NN=C1C QSUNKZHBZDXQPH-UHFFFAOYSA-N 0.000 claims 1
- FMAMGYIAROUURS-UHFFFAOYSA-N 6-(3-cyclopropyl-5-methyl-1,2-oxazol-4-yl)-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=CC2=C(C=CC(=O)N2CC2=NC=CC=C2)C=C1C1=C(C)ON=C1C1CC1 FMAMGYIAROUURS-UHFFFAOYSA-N 0.000 claims 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 claims 1
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 claims 1
- MVIRVQRPJWFQFE-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-(2-methoxyethoxy)-4-(pyridin-4-ylmethyl)-1,4-benzoxazin-3-one Chemical compound COCCOC1=CC2=C(OCC(=O)N2CC2=CC=NC=C2)C=C1C1=C(C)ON=C1C MVIRVQRPJWFQFE-UHFFFAOYSA-N 0.000 claims 1
- GVGQEJUUIVYHGF-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2,2-dimethyl-4-(pyridin-3-ylmethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OC(C(N2CC=2C=NC=CC2)=O)(C)C)C1)OC)C GVGQEJUUIVYHGF-UHFFFAOYSA-N 0.000 claims 1
- WWBWXXGSBBIKSZ-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(1-pyridin-2-ylethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2C(C)C2=NC=CC=C2)=O)C1)OC)C WWBWXXGSBBIKSZ-UHFFFAOYSA-N 0.000 claims 1
- AOLLZEZAXBKTKG-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(1-pyridin-3-ylethyl)-2,3-dihydro-1,4-benzoxazine Chemical compound COC1=C(C=C2OCCN(C(C)C3=CN=CC=C3)C2=C1)C1=C(C)ON=C1C AOLLZEZAXBKTKG-UHFFFAOYSA-N 0.000 claims 1
- ZTLTWOUDFXEURX-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(2-pyridin-2-ylethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CCC2=NC=CC=C2)=O)C1)OC)C ZTLTWOUDFXEURX-UHFFFAOYSA-N 0.000 claims 1
- USWRPOJBFQFOGA-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(oxan-4-ylmethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC2CCOCC2)=O)C1)OC)C USWRPOJBFQFOGA-UHFFFAOYSA-N 0.000 claims 1
- JTIGTMLFCHDXIB-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(pyridin-2-ylmethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC2=NC=CC=C2)=O)C1)OC)C JTIGTMLFCHDXIB-UHFFFAOYSA-N 0.000 claims 1
- XQSSIADMEFXDDV-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(pyridin-3-ylmethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC=2C=NC=CC2)=O)C1)OC)C XQSSIADMEFXDDV-UHFFFAOYSA-N 0.000 claims 1
- YYFREERCGBZTBH-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-(pyridin-4-ylmethyl)-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC2=CC=NC=C2)=O)C1)OC)C YYFREERCGBZTBH-UHFFFAOYSA-N 0.000 claims 1
- QXZSFPIOZGZLGG-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-[(1-propanoylpiperidin-4-yl)methyl]-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC2CCN(CC2)C(CC)=O)=O)C=1)OC)C QXZSFPIOZGZLGG-UHFFFAOYSA-N 0.000 claims 1
- OMHSCLZUADEVMJ-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-[(5-methoxypyridin-2-yl)methyl]-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC2=NC=C(C=C2)OC)=O)C1)OC)C OMHSCLZUADEVMJ-UHFFFAOYSA-N 0.000 claims 1
- BSUGZJCRMNQWLP-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-[(6-methoxypyridin-3-yl)methyl]-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC=2C=NC(=CC2)OC)=O)C1)OC)C BSUGZJCRMNQWLP-UHFFFAOYSA-N 0.000 claims 1
- RNFYYAMHDPPQOQ-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-[(6-methylpyridin-3-yl)methyl]-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC=2C=NC(=CC2)C)=O)C1)OC)C RNFYYAMHDPPQOQ-UHFFFAOYSA-N 0.000 claims 1
- MYKFOKLQXYJESP-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-4-[(6-oxo-1H-pyridin-3-yl)methyl]-1,4-benzoxazin-3-one Chemical compound CC1=NOC(=C1C=1C(=CC2=C(OCC(N2CC=2C=NC(=CC=2)O)=O)C=1)OC)C MYKFOKLQXYJESP-UHFFFAOYSA-N 0.000 claims 1
- SEWXUCBNVXLKFH-UHFFFAOYSA-N 7-[2-(dimethylamino)ethoxy]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CN(C)CCOC1=C(C=C2C=CC(=O)N(CC3=NC=CC=C3)C2=C1)C1=C(C)ON=C1C SEWXUCBNVXLKFH-UHFFFAOYSA-N 0.000 claims 1
- QPQADKUNPWKQER-UHFFFAOYSA-N 7-butoxy-6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound CCCCOC1=C(C=C2C=CC(=O)N(CC3=NC=CC=C3)C2=C1)C1=C(C)ON=C1C QPQADKUNPWKQER-UHFFFAOYSA-N 0.000 claims 1
- QBTPRMLUXFBHHQ-UHFFFAOYSA-N 7-methoxy-6-(3-methyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=CC(N(C2=C1)CC1=NC=CC=C1)=O)C=1C(=NOC1)C QBTPRMLUXFBHHQ-UHFFFAOYSA-N 0.000 claims 1
- YTYKYMMMBPRIIF-UHFFFAOYSA-N 7-methoxy-6-(4-methyl-2-oxo-1H-imidazol-3-yl)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=CC(N(C2=C1)CC1=NC=CC=C1)=O)N1C(NC=C1C)=O YTYKYMMMBPRIIF-UHFFFAOYSA-N 0.000 claims 1
- PVYLWRLORWMUAF-UHFFFAOYSA-N 7-methoxy-6-(5-methyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound COC1=C(C=C2C=CC(N(C2=C1)CC1=NC=CC=C1)=O)C=1C=NOC1C PVYLWRLORWMUAF-UHFFFAOYSA-N 0.000 claims 1
- KZWNLDGEKXZMPG-UHFFFAOYSA-N 7-methoxy-6-(6-oxo-1H-pyridin-3-yl)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound OC1=CC=C(C=N1)C=1C=C2C=CC(N(C2=CC1OC)CC1=NC=CC=C1)=O KZWNLDGEKXZMPG-UHFFFAOYSA-N 0.000 claims 1
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 claims 1
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 claims 1
- 229940126639 Compound 33 Drugs 0.000 claims 1
- 229940127007 Compound 39 Drugs 0.000 claims 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims 1
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 claims 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 claims 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 claims 1
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 claims 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims 1
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 claims 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 claims 1
- 125000005336 allyloxy group Chemical group 0.000 claims 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims 1
- 229940125797 compound 12 Drugs 0.000 claims 1
- 229940126543 compound 14 Drugs 0.000 claims 1
- 229940125758 compound 15 Drugs 0.000 claims 1
- 229940125782 compound 2 Drugs 0.000 claims 1
- 229940125810 compound 20 Drugs 0.000 claims 1
- 229940126086 compound 21 Drugs 0.000 claims 1
- 229940126208 compound 22 Drugs 0.000 claims 1
- 229940125833 compound 23 Drugs 0.000 claims 1
- 229940125961 compound 24 Drugs 0.000 claims 1
- 229940125846 compound 25 Drugs 0.000 claims 1
- 229940125851 compound 27 Drugs 0.000 claims 1
- 229940127204 compound 29 Drugs 0.000 claims 1
- 229940126214 compound 3 Drugs 0.000 claims 1
- 229940125877 compound 31 Drugs 0.000 claims 1
- 229940125878 compound 36 Drugs 0.000 claims 1
- 229940125807 compound 37 Drugs 0.000 claims 1
- 229940127573 compound 38 Drugs 0.000 claims 1
- 229940126540 compound 41 Drugs 0.000 claims 1
- 229940125936 compound 42 Drugs 0.000 claims 1
- 229940125844 compound 46 Drugs 0.000 claims 1
- 229940127271 compound 49 Drugs 0.000 claims 1
- 229940126545 compound 53 Drugs 0.000 claims 1
- 229940127113 compound 57 Drugs 0.000 claims 1
- 229940125900 compound 59 Drugs 0.000 claims 1
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 claims 1
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 claims 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 claims 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 claims 1
- FDBYIYFVSAHJLY-UHFFFAOYSA-N resmetirom Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(NC(=O)C(C#N)=N2)=O)Cl)=N1 FDBYIYFVSAHJLY-UHFFFAOYSA-N 0.000 claims 1
- 229940126585 therapeutic drug Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 description 152
- 238000003786 synthesis reaction Methods 0.000 description 149
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 131
- 239000011541 reaction mixture Substances 0.000 description 116
- 239000000243 solution Substances 0.000 description 112
- 238000005481 NMR spectroscopy Methods 0.000 description 107
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 95
- 239000007787 solid Substances 0.000 description 91
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 84
- 238000006243 chemical reaction Methods 0.000 description 83
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 235000019439 ethyl acetate Nutrition 0.000 description 59
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 57
- 239000012267 brine Substances 0.000 description 56
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 56
- 229910052938 sodium sulfate Inorganic materials 0.000 description 55
- 235000011152 sodium sulphate Nutrition 0.000 description 55
- 238000000034 method Methods 0.000 description 53
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 33
- 238000000746 purification Methods 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 239000011734 sodium Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 238000012746 preparative thin layer chromatography Methods 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000000460 chlorine Substances 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- 208000035475 disorder Diseases 0.000 description 11
- 239000005457 ice water Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 0 CC(C)(C(Nc1c2)=*)Oc1ccc2OC Chemical compound CC(C)(C(Nc1c2)=*)Oc1ccc2OC 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
- 230000002265 prevention Effects 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000010511 deprotection reaction Methods 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000000376 reactant Substances 0.000 description 7
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 7
- 108010033040 Histones Proteins 0.000 description 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 238000010926 purge Methods 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 125000001246 bromo group Chemical group Br* 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- KQNBRMUBPRGXSL-UHFFFAOYSA-N 1-(bromomethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1 KQNBRMUBPRGXSL-UHFFFAOYSA-N 0.000 description 4
- RUTNWXBHRAIQSP-UHFFFAOYSA-N 4-bromo-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1Br RUTNWXBHRAIQSP-UHFFFAOYSA-N 0.000 description 4
- WBQYJBJBDHZIHC-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)quinoline-3-carbaldehyde Chemical compound CC1=NOC(=C1C=1C=C2C=C(C(N(C2=CC1OC)CC1=NC=CC=C1)=O)C=O)C WBQYJBJBDHZIHC-UHFFFAOYSA-N 0.000 description 4
- JDIGACDXGSEITA-UHFFFAOYSA-N 6-bromo-7-methoxy-3-methyl-1H-quinolin-2-one Chemical compound BrC=1C=C2C=C(C(NC2=CC1OC)=O)C JDIGACDXGSEITA-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 102100033641 Bromodomain-containing protein 2 Human genes 0.000 description 4
- 102100033642 Bromodomain-containing protein 3 Human genes 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 208000007514 Herpes zoster Diseases 0.000 description 4
- 101000871850 Homo sapiens Bromodomain-containing protein 2 Proteins 0.000 description 4
- 101000871851 Homo sapiens Bromodomain-containing protein 3 Proteins 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 208000010718 Multiple Organ Failure Diseases 0.000 description 4
- 238000007126 N-alkylation reaction Methods 0.000 description 4
- 206010033645 Pancreatitis Diseases 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 206010040047 Sepsis Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Inorganic materials [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 150000003456 sulfonamides Chemical class 0.000 description 4
- IRFHMTUHTBSEBK-QGZVFWFLSA-N tert-butyl n-[(2s)-2-(2,5-difluorophenyl)-3-quinolin-3-ylpropyl]carbamate Chemical compound C1([C@H](CC=2C=C3C=CC=CC3=NC=2)CNC(=O)OC(C)(C)C)=CC(F)=CC=C1F IRFHMTUHTBSEBK-QGZVFWFLSA-N 0.000 description 4
- ZBPRUZRYHWEEEK-UHFFFAOYSA-N (3,5-dimethyl-2h-1,2-oxazol-3-yl)boronic acid Chemical compound CC1=CC(C)(B(O)O)NO1 ZBPRUZRYHWEEEK-UHFFFAOYSA-N 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 3
- TUADYTFWZPZZTP-UHFFFAOYSA-N 2-amino-4-methoxyphenol Chemical compound COC1=CC=C(O)C(N)=C1 TUADYTFWZPZZTP-UHFFFAOYSA-N 0.000 description 3
- FBXGQDUVJBKEAJ-UHFFFAOYSA-N 4h-oxazin-3-one Chemical compound O=C1CC=CON1 FBXGQDUVJBKEAJ-UHFFFAOYSA-N 0.000 description 3
- USFWYXXZVZDJBT-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1H-quinoxalin-2-one Chemical compound CC1=NOC(=C1C=1C=C2N=CC(NC2=CC1OC)=O)C USFWYXXZVZDJBT-UHFFFAOYSA-N 0.000 description 3
- UDADXUSRFOGIMR-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3,4-dihydro-1H-quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2CCC(NC2=CC1OC)=O)C UDADXUSRFOGIMR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
- 108091005575 Bromodomain-containing proteins Proteins 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- 206010047115 Vasculitis Diseases 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminum chloride Substances Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 210000003483 chromatin Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 201000008383 nephritis Diseases 0.000 description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl chloride Substances ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 3
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 3
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Substances [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 3
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N sodium azide Substances [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N sodium methoxide Substances [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Substances [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- XQDANBKPALOMEF-HYXAFXHYSA-N (nz)-n-(cyclopropylmethylidene)hydroxylamine Chemical compound O\N=C/C1CC1 XQDANBKPALOMEF-HYXAFXHYSA-N 0.000 description 2
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
- CPFLWFFGELPZFS-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3-methyl-2-oxoquinoline-4-carbonitrile Chemical compound COC1=CC2=C(C=C1C1=C(C)ON=C1C)C(C#N)=C(C)C(=O)N2CCC1=CC=C(Cl)C=C1 CPFLWFFGELPZFS-UHFFFAOYSA-N 0.000 description 2
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 2
- AZNKKZHZGDZSIF-UHFFFAOYSA-N 1-fluoro-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1F AZNKKZHZGDZSIF-UHFFFAOYSA-N 0.000 description 2
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
- SKJQCBCAMCHGTR-UHFFFAOYSA-N 2-[(7-bromo-6-methoxy-2,3-dihydro-1,4-benzoxazin-4-yl)methyl]aniline Chemical compound COC1=CC2=C(OCCN2CC2=C(N)C=CC=C2)C=C1Br SKJQCBCAMCHGTR-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- WRXZCLBKDXISQA-UHFFFAOYSA-N 2-chloro-7-methoxyquinoline-3-carbaldehyde Chemical compound C1=C(C=O)C(Cl)=NC2=CC(OC)=CC=C21 WRXZCLBKDXISQA-UHFFFAOYSA-N 0.000 description 2
- YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 2
- AKTDHHFJFNIILG-UHFFFAOYSA-N 3,3-diethoxypropanoic acid Chemical compound CCOC(CC(O)=O)OCC AKTDHHFJFNIILG-UHFFFAOYSA-N 0.000 description 2
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 2
- IIKSVIKTCKJDHC-UHFFFAOYSA-N 3-cyclopropyl-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-oxazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=C(C)ON=C1C1CC1 IIKSVIKTCKJDHC-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- IVZCMVDKWYJIRR-UHFFFAOYSA-N 5-(3,5-dimethyl-1,2-oxazol-4-yl)-4-methoxy-2-nitroaniline Chemical compound CC1=NOC(=C1C=1C(=CC(=C(N)C1)[N+](=O)[O-])OC)C IVZCMVDKWYJIRR-UHFFFAOYSA-N 0.000 description 2
- SDMPVXWZPAGMHL-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2,4-triazol-4-yl)-7-methoxy-1H-quinolin-2-one Chemical compound COC1=CC2=C(C=CC(=O)N2)C=C1N1C(C)=NN=C1C SDMPVXWZPAGMHL-UHFFFAOYSA-N 0.000 description 2
- OTPAWUNZUYIPGN-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-1H-quinolin-2-one Chemical compound CC1=NOC(=C1C=1C=C2C=CC(NC2=CC1OC)=O)C OTPAWUNZUYIPGN-UHFFFAOYSA-N 0.000 description 2
- YHXXTFPMZDBZLD-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-piperidin-4-yloxy-1-(pyridin-2-ylmethyl)quinolin-2-one hydrochloride Chemical compound Cl.Cc1noc(C)c1-c1cc2ccc(=O)n(Cc3ccccn3)c2cc1OC1CCNCC1 YHXXTFPMZDBZLD-UHFFFAOYSA-N 0.000 description 2
- BYKVIUJYKSJPTJ-UHFFFAOYSA-N 6-amino-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound NC=1C=C2C=CC(N(C2=CC1OC)CC1=NC=CC=C1)=O BYKVIUJYKSJPTJ-UHFFFAOYSA-N 0.000 description 2
- OALNTHXAGQPBBT-UHFFFAOYSA-N 6-bromo-7-methoxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C=C(OC)C(Br)=C2 OALNTHXAGQPBBT-UHFFFAOYSA-N 0.000 description 2
- ABSBEBURKBJDQR-UHFFFAOYSA-N 6-bromo-7-methoxy-2-oxo-1-(pyridin-2-ylmethyl)quinoline-3-carbaldehyde Chemical compound COC1=CC2=C(C=C1Br)C=C(C=O)C(=O)N2CC1=NC=CC=C1 ABSBEBURKBJDQR-UHFFFAOYSA-N 0.000 description 2
- SORMLBIPZYTQQX-UHFFFAOYSA-N 6-bromo-7-methoxy-3,3-dimethyl-1,4-dihydroquinolin-2-one Chemical compound BrC=1C=C2CC(C(NC2=CC1OC)=O)(C)C SORMLBIPZYTQQX-UHFFFAOYSA-N 0.000 description 2
- ZAQPGHIBZMLYAG-UHFFFAOYSA-N 6-bromo-7-methoxy-3,3-dimethyl-1H-quinoline-2,4-dione Chemical compound COC1=CC2=C(C=C1Br)C(=O)C(C)(C)C(=O)N2 ZAQPGHIBZMLYAG-UHFFFAOYSA-N 0.000 description 2
- YTQMEXALSFUJAU-UHFFFAOYSA-N 6-bromo-7-methoxy-4,4-dimethyl-1,3-dihydroquinolin-2-one Chemical compound BrC=1C=C2C(CC(NC2=CC1OC)=O)(C)C YTQMEXALSFUJAU-UHFFFAOYSA-N 0.000 description 2
- PNMLUEOZAOOPDK-UHFFFAOYSA-N 6-bromo-7-methoxy-4-methyl-1H-quinolin-2-one Chemical compound BrC=1C=C2C(=CC(NC2=CC1OC)=O)C PNMLUEOZAOOPDK-UHFFFAOYSA-N 0.000 description 2
- PGYXUPDGRCMQBU-UHFFFAOYSA-N 6-isocyanato-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound N(=C=O)C=1C=C2C=CC(N(C2=CC1OC)CC1=NC=CC=C1)=O PGYXUPDGRCMQBU-UHFFFAOYSA-N 0.000 description 2
- OBIDASABDZLQMU-UHFFFAOYSA-N 7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-3,4-dihydro-2H-1,4-benzoxazine Chemical compound COC1=CC2=C(OCCN2)C=C1C1=C(C)ON=C1C OBIDASABDZLQMU-UHFFFAOYSA-N 0.000 description 2
- BSBWSUMJGPLAFP-UHFFFAOYSA-N 7-[bromo(difluoro)methoxy]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound BrC(OC1=C(C=C2C=CC(N(C2=C1)CC1=NC=CC=C1)=O)C=1C(=NOC1C)C)(F)F BSBWSUMJGPLAFP-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VWVKUNOPTJGDOB-BDHVOXNPSA-N Anhydrous tofogliflozin Chemical compound C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 VWVKUNOPTJGDOB-BDHVOXNPSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010077544 Chromatin Proteins 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 208000037487 Endotoxemia Diseases 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 208000007465 Giant cell arteritis Diseases 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 208000009889 Herpes Simplex Diseases 0.000 description 2
- 241000701806 Human papillomavirus Species 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical compound O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 206010033647 Pancreatitis acute Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 206010053879 Sepsis syndrome Diseases 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 206010069351 acute lung injury Diseases 0.000 description 2
- 201000003229 acute pancreatitis Diseases 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- RYPKRALMXUUNKS-UHFFFAOYSA-N hex-2-ene Chemical compound CCCC=CC RYPKRALMXUUNKS-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- FOVVWLNYGMVMIW-UHFFFAOYSA-N n-(4-bromo-3-methoxyphenyl)acetamide Chemical compound COC1=CC(NC(C)=O)=CC=C1Br FOVVWLNYGMVMIW-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- QMMOXUPEWRXHJS-UHFFFAOYSA-N pent-2-ene Chemical compound CCC=CC QMMOXUPEWRXHJS-UHFFFAOYSA-N 0.000 description 2
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 206010043207 temporal arteritis Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- DIVNUTGTTIRPQA-UHFFFAOYSA-N (3,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1OC DIVNUTGTTIRPQA-UHFFFAOYSA-N 0.000 description 1
- DFLZHCRDZKKMEZ-CMDGGOBGSA-N (E)-N-[4-(3,5-dimethyl-1,2,4-triazol-4-yl)-3-methoxyphenyl]-3-ethoxyprop-2-enamide Chemical compound CCO\C=C\C(=O)NC1=CC(OC)=C(C=C1)N1C(C)=NN=C1C DFLZHCRDZKKMEZ-CMDGGOBGSA-N 0.000 description 1
- YXKFWXKUHONLIB-CMDGGOBGSA-N (E)-N-[4-(3,5-dimethyl-1,2-oxazol-4-yl)-3-methoxyphenyl]-3-ethoxyprop-2-enamide Chemical compound CC1=NOC(=C1C1=C(C=C(C=C1)NC(\C=C\OCC)=O)OC)C YXKFWXKUHONLIB-CMDGGOBGSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- ZTVILFGCSUSCKF-UHFFFAOYSA-N 1,2-dihydroquinoline-3-carbaldehyde Chemical compound C1=CC=C2NCC(C=O)=CC2=C1 ZTVILFGCSUSCKF-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- ADASULLEMKLQKU-UHFFFAOYSA-N 1-(7-bromo-6-methoxy-2,3-dihydro-1,4-benzoxazin-4-yl)ethanone Chemical compound COC1=CC2=C(OCCN2C(C)=O)C=C1Br ADASULLEMKLQKU-UHFFFAOYSA-N 0.000 description 1
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 1
- ICFNQSJFXTVWNV-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-3-(hydroxymethyl)-7-methoxyquinolin-2-one Chemical compound ClC1=CC=C(C=C1)CCN1C(C(=CC2=CC(=C(C=C12)OC)C=1C(=NOC1C)C)CO)=O ICFNQSJFXTVWNV-UHFFFAOYSA-N 0.000 description 1
- FLZIMSYUSHTVBY-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)ethyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-2-oxoquinoline-3-carbaldehyde Chemical compound COC1=CC2=C(C=C(C=O)C(=O)N2CCC2=CC=C(Cl)C=C2)C=C1C1=C(C)ON=C1C FLZIMSYUSHTVBY-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- JRXCUTAHLPYHAY-UHFFFAOYSA-N 1-ethylquinolin-2-one Chemical compound C1=CC=C2C=CC(=O)N(CC)C2=C1 JRXCUTAHLPYHAY-UHFFFAOYSA-N 0.000 description 1
- DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
- MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- QYEMNJMSULGQRD-UHFFFAOYSA-N 1-methyl-2-quinolone Chemical compound C1=CC=C2C=CC(=O)N(C)C2=C1 QYEMNJMSULGQRD-UHFFFAOYSA-N 0.000 description 1
- FGYADSCZTQOAFK-UHFFFAOYSA-N 1-methylbenzimidazole Chemical compound C1=CC=C2N(C)C=NC2=C1 FGYADSCZTQOAFK-UHFFFAOYSA-N 0.000 description 1
- AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
- OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 description 1
- HLNRRPIYRBBHSQ-UHFFFAOYSA-N 1-propylpyrrolidine Chemical compound CCCN1CCCC1 HLNRRPIYRBBHSQ-UHFFFAOYSA-N 0.000 description 1
- HVOAMIOKNARIMR-UHFFFAOYSA-N 1-pyridin-4-ylethanol Chemical compound CC(O)C1=CC=NC=C1 HVOAMIOKNARIMR-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
- JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
- HONBHDVWFSRHMU-UHFFFAOYSA-N 2-(iodomethyl)-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=C(CI)N=C1 HONBHDVWFSRHMU-UHFFFAOYSA-N 0.000 description 1
- KPTUFHHCSRDDDG-UHFFFAOYSA-N 2-[1-[2-(4-chlorophenyl)ethyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-2-oxoquinolin-3-yl]acetonitrile Chemical compound ClC1=CC=C(C=C1)CCN1C(C(=CC2=CC(=C(C=C12)OC)C=1C(=NOC1C)C)CC#N)=O KPTUFHHCSRDDDG-UHFFFAOYSA-N 0.000 description 1
- SKCNYHLTRZIINA-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)pyridine Chemical compound ClCC1=CC=C(Cl)N=C1 SKCNYHLTRZIINA-UHFFFAOYSA-N 0.000 description 1
- WFRLFZAMCVAQLN-UHFFFAOYSA-N 2-fluoro-5-nitrophenol Chemical compound OC1=CC([N+]([O-])=O)=CC=C1F WFRLFZAMCVAQLN-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- INSUSOZBMWJGDG-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazol-4-amine Chemical compound CC1=NOC(C)=C1N INSUSOZBMWJGDG-UHFFFAOYSA-N 0.000 description 1
- IJEUISLJVBUNRE-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C)=C1C(O)=O IJEUISLJVBUNRE-UHFFFAOYSA-N 0.000 description 1
- SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
- GNUDAJTUCJEBEI-UHFFFAOYSA-N 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound CC1=NNC(C)=C1B1OC(C)(C)C(C)(C)O1 GNUDAJTUCJEBEI-UHFFFAOYSA-N 0.000 description 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZFCJLBDBHFBSEX-UHFFFAOYSA-N 3-bromo-1-[(3,4-dimethoxyphenyl)methyl]-4-methylpyrrole-2,5-dione Chemical compound C1=C(OC)C(OC)=CC=C1CN1C(=O)C(Br)=C(C)C1=O ZFCJLBDBHFBSEX-UHFFFAOYSA-N 0.000 description 1
- IGTIATLQSPRHCG-UHFFFAOYSA-N 3-bromo-4-methylfuran-2,5-dione 3-methylfuran-2,5-dione Chemical compound CC=1C(OC(C1)=O)=O.BrC=1C(OC(C1C)=O)=O IGTIATLQSPRHCG-UHFFFAOYSA-N 0.000 description 1
- OINWZUJVEXUHCC-UHFFFAOYSA-N 3-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=CC(S(Cl)(=O)=O)=C1 OINWZUJVEXUHCC-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- BDUBTLFQHNYXPC-UHFFFAOYSA-N 3-methylbut-2-enoyl chloride Chemical compound CC(C)=CC(Cl)=O BDUBTLFQHNYXPC-UHFFFAOYSA-N 0.000 description 1
- ZLPORNPZJNRGCO-UHFFFAOYSA-N 3-methylpyrrole-2,5-dione Chemical compound CC1=CC(=O)NC1=O ZLPORNPZJNRGCO-UHFFFAOYSA-N 0.000 description 1
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
- FDQYQNRFYLSJOP-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-prop-1-ynyl-1,3,2-dioxaborolane Chemical compound CC#CB1OC(C)(C)C(C)(C)O1 FDQYQNRFYLSJOP-UHFFFAOYSA-N 0.000 description 1
- MRWWWZLJWNIEEJ-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-propan-2-yloxy-1,3,2-dioxaborolane Chemical compound CC(C)OB1OC(C)(C)C(C)(C)O1 MRWWWZLJWNIEEJ-UHFFFAOYSA-N 0.000 description 1
- DBZUMNBGSJPAJD-UHFFFAOYSA-N 4-(3,5-dimethyl-1,2,4-triazol-4-yl)-3-methoxyaniline Chemical compound COC1=C(C=CC(N)=C1)N1C(C)=NN=C1C DBZUMNBGSJPAJD-UHFFFAOYSA-N 0.000 description 1
- VSZKAKBHWHBKNQ-UHFFFAOYSA-N 4-(3,5-dimethyl-1,2-oxazol-4-yl)-3-methoxyaniline Chemical compound CC1=NOC(=C1C1=C(C=C(N)C=C1)OC)C VSZKAKBHWHBKNQ-UHFFFAOYSA-N 0.000 description 1
- KRLKXOLFFQWKPZ-UHFFFAOYSA-N 4-(bromomethyl)pyridine Chemical compound BrCC1=CC=NC=C1 KRLKXOLFFQWKPZ-UHFFFAOYSA-N 0.000 description 1
- AROGQTWAAJTEFR-UHFFFAOYSA-N 4-(chloromethyl)pyrimidine Chemical compound ClCC1=CC=NC=N1 AROGQTWAAJTEFR-UHFFFAOYSA-N 0.000 description 1
- YFOZFRSXXCDLIL-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-6-methoxy-7-nitro-1,4-benzoxazin-3-one Chemical compound COC1=CC2=C(OCC(=O)N2CC2=CC=C(Cl)C=C2)C=C1[N+]([O-])=O YFOZFRSXXCDLIL-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
- KLTDQLIGNSBZPO-UHFFFAOYSA-N 4-methoxy-2-nitrobenzaldehyde Chemical compound COC1=CC=C(C=O)C([N+]([O-])=O)=C1 KLTDQLIGNSBZPO-UHFFFAOYSA-N 0.000 description 1
- YBUGOACXDPDUIR-UHFFFAOYSA-N 4-methoxy-2-nitrophenol Chemical compound COC1=CC=C(O)C([N+]([O-])=O)=C1 YBUGOACXDPDUIR-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- QRCGFTXRXYMJOS-UHFFFAOYSA-N 4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(=O)COC2=C1 QRCGFTXRXYMJOS-UHFFFAOYSA-N 0.000 description 1
- HQUCUBOXGLEYNA-UHFFFAOYSA-N 5-bromo-4-methoxy-2-nitroaniline Chemical compound COC1=CC([N+]([O-])=O)=C(N)C=C1Br HQUCUBOXGLEYNA-UHFFFAOYSA-N 0.000 description 1
- JJBJUKDFTLCVOX-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-(piperidin-4-ylmethoxy)-1-(pyridin-2-ylmethyl)quinolin-2-one hydrochloride Chemical compound Cl.Cc1noc(C)c1-c1cc2ccc(=O)n(Cc3ccccn3)c2cc1OCC1CCNCC1 JJBJUKDFTLCVOX-UHFFFAOYSA-N 0.000 description 1
- HDAOEPSBMIKPEM-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-7-methoxy-3,4-dihydro-1H-quinoxalin-2-one Chemical compound CC1=NOC(=C1C=1C=C2NCC(NC2=CC1OC)=O)C HDAOEPSBMIKPEM-UHFFFAOYSA-N 0.000 description 1
- FYOMVBPKEQSTSO-UHFFFAOYSA-N 6-bromo-1-[(6-chloropyridin-3-yl)methyl]-7-methoxyquinolin-2-one Chemical compound BrC=1C=C2C=CC(N(C2=CC1OC)CC=1C=NC(=CC1)Cl)=O FYOMVBPKEQSTSO-UHFFFAOYSA-N 0.000 description 1
- FUJXIYNXRSKPHY-UHFFFAOYSA-N 6-bromo-1-[2-(4-chlorophenyl)ethyl]-7-methoxy-2-oxoquinoline-3-carbaldehyde Chemical compound COC1=CC2=C(C=C1Br)C=C(C=O)C(=O)N2CCC1=CC=C(Cl)C=C1 FUJXIYNXRSKPHY-UHFFFAOYSA-N 0.000 description 1
- HHYHHFOXBHIFKE-UHFFFAOYSA-N 6-bromo-2-chloro-7-methoxyquinoline-3-carbaldehyde Chemical compound BrC=1C=C2C=C(C(=NC2=CC1OC)Cl)C=O HHYHHFOXBHIFKE-UHFFFAOYSA-N 0.000 description 1
- HXUDURSUYQWSOY-UHFFFAOYSA-N 6-bromo-3-cyclohexyl-7-methoxy-1H-quinolin-2-one Chemical compound BrC=1C=C2C=C(C(NC2=CC1OC)=O)C1CCCCC1 HXUDURSUYQWSOY-UHFFFAOYSA-N 0.000 description 1
- WYOOKLVWUVBNQJ-UHFFFAOYSA-N 6-bromo-7-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C=C(O)C(Br)=C2 WYOOKLVWUVBNQJ-UHFFFAOYSA-N 0.000 description 1
- KUTAQJGGGVUIQF-UHFFFAOYSA-N 6-bromo-7-methoxy-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound BrC=1C=C2C=CC(N(C2=CC1OC)CC1=NC=CC=C1)=O KUTAQJGGGVUIQF-UHFFFAOYSA-N 0.000 description 1
- FNZGGIJNQXNCAP-UHFFFAOYSA-N 6-bromo-7-methoxy-1-(pyrimidin-4-ylmethyl)quinolin-2-one Chemical compound BrC=1C=C2C=CC(N(C2=CC1OC)CC1=NC=NC=C1)=O FNZGGIJNQXNCAP-UHFFFAOYSA-N 0.000 description 1
- YWGRZAGXNFIQBO-UHFFFAOYSA-N 6-methoxy-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=CC(OC)=CC=C21 YWGRZAGXNFIQBO-UHFFFAOYSA-N 0.000 description 1
- PKAUOZNREDGOAP-UHFFFAOYSA-N 6-methoxy-7-nitro-4H-1,4-benzoxazin-3-one Chemical compound COC1=CC2=C(OCC(=O)N2)C=C1[N+]([O-])=O PKAUOZNREDGOAP-UHFFFAOYSA-N 0.000 description 1
- QVCKHHFGNXCYKZ-UHFFFAOYSA-N 7-amino-4-[(4-chlorophenyl)methyl]-6-methoxy-1,4-benzoxazin-3-one Chemical compound COC1=CC2=C(OCC(=O)N2CC2=CC=C(Cl)C=C2)C=C1N QVCKHHFGNXCYKZ-UHFFFAOYSA-N 0.000 description 1
- FZQFGZXULYFWNM-UHFFFAOYSA-N 7-bromo-4-[(4-chlorophenyl)methyl]-6-methoxy-1,4-benzoxazin-3-one Chemical compound COC1=CC2=C(OCC(=O)N2CC2=CC=C(Cl)C=C2)C=C1Br FZQFGZXULYFWNM-UHFFFAOYSA-N 0.000 description 1
- SPCLOJHEMWDFCX-UHFFFAOYSA-N 7-bromo-6-methoxy-2,2-dimethyl-4H-1,4-benzoxazin-3-one Chemical compound COC1=CC2=C(OC(C)(C)C(=O)N2)C=C1Br SPCLOJHEMWDFCX-UHFFFAOYSA-N 0.000 description 1
- HYPXPTICMYBXMR-UHFFFAOYSA-N 7-bromo-6-methoxy-3,4-dihydro-2H-1,4-benzoxazine Chemical compound COC1=CC2=C(OCCN2)C=C1Br HYPXPTICMYBXMR-UHFFFAOYSA-N 0.000 description 1
- QDNKMPHSGLTLCM-UHFFFAOYSA-N 7-bromo-6-methoxy-4-(pyridin-4-ylmethyl)-1,4-benzoxazin-3-one Chemical compound BrC=1C(=CC2=C(OCC(N2CC2=CC=NC=C2)=O)C=1)OC QDNKMPHSGLTLCM-UHFFFAOYSA-N 0.000 description 1
- HTDAAJOAKFEKLH-UHFFFAOYSA-N 7-bromo-6-methoxy-4-[(2-nitrophenyl)methyl]-2,3-dihydro-1,4-benzoxazine Chemical compound COC1=CC2=C(OCCN2CC2=C(C=CC=C2)[N+]([O-])=O)C=C1Br HTDAAJOAKFEKLH-UHFFFAOYSA-N 0.000 description 1
- BZQKTEZRBOTPEW-UHFFFAOYSA-N 7-bromo-6-methoxy-4H-1,4-benzoxazin-3-one Chemical compound COC1=CC2=C(OCC(=O)N2)C=C1Br BZQKTEZRBOTPEW-UHFFFAOYSA-N 0.000 description 1
- VUKFTGRTRKQOKY-UHFFFAOYSA-N 7-methoxy-2-oxo-1h-quinoline-3-carbaldehyde Chemical compound C1=C(C=O)C(=O)NC2=CC(OC)=CC=C21 VUKFTGRTRKQOKY-UHFFFAOYSA-N 0.000 description 1
- XAIMRDABVGYGMC-UHFFFAOYSA-N 7-methoxy-6-(6-phenylmethoxypyridin-3-yl)-1-(pyridin-2-ylmethyl)quinolin-2-one Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=N1)C=1C=C2C=CC(N(C2=CC1OC)CC1=NC=CC=C1)=O XAIMRDABVGYGMC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 241000701386 African swine fever virus Species 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- TUXKRWWQDITKKZ-UHFFFAOYSA-N BrCC(=O)OCC.C(C)(=O)O Chemical compound BrCC(=O)OCC.C(C)(=O)O TUXKRWWQDITKKZ-UHFFFAOYSA-N 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- MTNLGPPDDFSXLB-UHFFFAOYSA-N CC(C)(Cc(c(N1)c2)cc(CBr)c2OC)C1=O Chemical compound CC(C)(Cc(c(N1)c2)cc(CBr)c2OC)C1=O MTNLGPPDDFSXLB-UHFFFAOYSA-N 0.000 description 1
- LJPLBYODAFQDDE-UHFFFAOYSA-N CC1(OB(OC1(C)C)B1OC(C(O1)(C)C)(C)C)C.O1CCOCC1 Chemical compound CC1(OB(OC1(C)C)B1OC(C(O1)(C)C)(C)C)C.O1CCOCC1 LJPLBYODAFQDDE-UHFFFAOYSA-N 0.000 description 1
- STHSJPMXSDZJPL-UHFFFAOYSA-N CNc(cc(cc1)[U]C)c1O Chemical compound CNc(cc(cc1)[U]C)c1O STHSJPMXSDZJPL-UHFFFAOYSA-N 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000000668 Chronic Pancreatitis Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 102000003893 Histone acetyltransferases Human genes 0.000 description 1
- 108090000246 Histone acetyltransferases Proteins 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000598171 Human adenovirus sp. Species 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000001940 Massive Hepatic Necrosis Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000003926 Myelitis Diseases 0.000 description 1
- 206010028594 Myocardial fibrosis Diseases 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- VEYYWZRYIYDQJM-ZETCQYMHSA-N N(2)-acetyl-L-lysine Chemical group CC(=O)N[C@H](C([O-])=O)CCCC[NH3+] VEYYWZRYIYDQJM-ZETCQYMHSA-N 0.000 description 1
- CCPRTAOSTKWKBQ-UHFFFAOYSA-N N-(4-bromo-3-methoxyphenyl)-3-methylbut-2-enamide Chemical compound BrC1=C(C=C(C=C1)NC(C=C(C)C)=O)OC CCPRTAOSTKWKBQ-UHFFFAOYSA-N 0.000 description 1
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
- XBKSXCBSCUGYJU-UHFFFAOYSA-N N-hydroxycyclopropanecarboximidoyl chloride Chemical compound ON=C(C1CC1)Cl XBKSXCBSCUGYJU-UHFFFAOYSA-N 0.000 description 1
- UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000034179 Neoplasms, Glandular and Epithelial Diseases 0.000 description 1
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 206010033649 Pancreatitis chronic Diseases 0.000 description 1
- 208000009608 Papillomavirus Infections Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000005585 Poxviridae Infections Diseases 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 206010039705 Scleritis Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000519995 Stachys sylvatica Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000001106 Takayasu Arteritis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- GVAFEGOUIQFLQH-UHFFFAOYSA-N [5-(trifluoromethyl)pyridin-2-yl]methanol Chemical compound OCC1=CC=C(C(F)(F)F)C=N1 GVAFEGOUIQFLQH-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Substances CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Substances BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 208000019748 bullous skin disease Diseases 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- ARQRPTNYUOLOGH-UHFFFAOYSA-N chcl3 chloroform Chemical compound ClC(Cl)Cl.ClC(Cl)Cl ARQRPTNYUOLOGH-UHFFFAOYSA-N 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 201000003740 cowpox Diseases 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000020335 dealkylation Effects 0.000 description 1
- 238000006900 dealkylation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- CZAHNRJVOPWAKN-VQHVLOKHSA-N ethyl (E)-3-(2-amino-4-methoxyphenyl)-2-methylprop-2-enoate Chemical compound NC1=C(C=CC(=C1)OC)/C=C(/C(=O)OCC)C CZAHNRJVOPWAKN-VQHVLOKHSA-N 0.000 description 1
- KFWFSHNVIDWUFA-VQHVLOKHSA-N ethyl (E)-3-(4-methoxy-2-nitrophenyl)-2-methylprop-2-enoate Chemical compound COC1=CC(=C(C=C1)/C=C(/C(=O)OCC)C)[N+](=O)[O-] KFWFSHNVIDWUFA-VQHVLOKHSA-N 0.000 description 1
- KZENFXVDPUMQOE-UHFFFAOYSA-N ethyl 2-(triphenyl-$l^{5}-phosphanylidene)propanoate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C(C)C(=O)OCC)C1=CC=CC=C1 KZENFXVDPUMQOE-UHFFFAOYSA-N 0.000 description 1
- SIALOQYKFQEKOG-UHFFFAOYSA-N ethyl 3,3-diethoxypropanoate Chemical compound CCOC(OCC)CC(=O)OCC SIALOQYKFQEKOG-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 208000021145 human papilloma virus infection Diseases 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Substances [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 201000008806 mesenchymal cell neoplasm Diseases 0.000 description 1
- IYBZURXLWKIMGI-UHFFFAOYSA-N methane;methanesulfonyl chloride Chemical compound C.CS(Cl)(=O)=O IYBZURXLWKIMGI-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- TWYRVVFQLQEJLP-UHFFFAOYSA-N methyl 3-(5-bromo-4-methoxy-2-nitrophenyl)-2-cyclohexyl-3-hydroxypropanoate Chemical compound BrC=1C(=CC(=C(C=1)C(C(C(=O)OC)C1CCCCC1)O)[N+](=O)[O-])OC TWYRVVFQLQEJLP-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- OIEFZHJNURGFFI-UHFFFAOYSA-N n-(3-methoxyphenyl)acetamide Chemical compound COC1=CC=CC(NC(C)=O)=C1 OIEFZHJNURGFFI-UHFFFAOYSA-N 0.000 description 1
- GBLCYDCYYSJHQE-UHFFFAOYSA-N n-(4-bromo-3-methoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(NC(=O)CC(C)=O)=CC=C1Br GBLCYDCYYSJHQE-UHFFFAOYSA-N 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- SEEYREPSKCQBBF-UHFFFAOYSA-N n-methylmaleimide Chemical compound CN1C(=O)C=CC1=O SEEYREPSKCQBBF-UHFFFAOYSA-N 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- WGRULTCAYDOGQK-UHFFFAOYSA-M sodium;sodium;hydroxide Chemical compound [OH-].[Na].[Na+] WGRULTCAYDOGQK-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- GNLNGVZPEKSDAR-UHFFFAOYSA-N tert-butyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate Chemical compound CC1=NN(C(=O)OC(C)(C)C)C(C)=C1B1OC(C)(C)C(C)(C)O1 GNLNGVZPEKSDAR-UHFFFAOYSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- IAQRGUVFOMOMEM-ONEGZZNKSA-N trans-but-2-ene Chemical compound C\C=C\C IAQRGUVFOMOMEM-ONEGZZNKSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- WIAMOTQUYWWPCK-UHFFFAOYSA-N trimethyl-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethynyl]silane Chemical compound CC1(C)OB(C#C[Si](C)(C)C)OC1(C)C WIAMOTQUYWWPCK-UHFFFAOYSA-N 0.000 description 1
- FEKWCCAGDIHLNS-UHFFFAOYSA-N trimethyl-[3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-oxazol-5-yl]silane Chemical compound CC1=NOC([Si](C)(C)C)=C1B1OC(C)(C)C(C)(C)O1 FEKWCCAGDIHLNS-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/536—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN125CH2014 | 2014-01-09 | ||
IN125/CHE/2014 | 2014-01-09 | ||
PCT/IB2015/050090 WO2015104653A1 (en) | 2014-01-09 | 2015-01-06 | Bicyclic heterocyclic derivatives as bromodomain inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017502057A JP2017502057A (ja) | 2017-01-19 |
JP6480944B2 true JP6480944B2 (ja) | 2019-03-13 |
Family
ID=52462967
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016545312A Active JP6480944B2 (ja) | 2014-01-09 | 2015-01-06 | ブロモドメイン阻害剤としての二環式複素環誘導体 |
Country Status (30)
Country | Link |
---|---|
US (2) | US10077259B2 (pt) |
EP (1) | EP3092227B1 (pt) |
JP (1) | JP6480944B2 (pt) |
KR (1) | KR102394518B1 (pt) |
CN (1) | CN106061966B (pt) |
AU (1) | AU2015205339B2 (pt) |
BR (1) | BR112016015311B1 (pt) |
CA (1) | CA2934788C (pt) |
CL (1) | CL2016001737A1 (pt) |
CY (1) | CY1122046T1 (pt) |
DK (1) | DK3092227T3 (pt) |
EA (1) | EA029224B1 (pt) |
ES (1) | ES2687497T3 (pt) |
HR (1) | HRP20181650T1 (pt) |
HU (1) | HUE041546T2 (pt) |
IL (1) | IL246140B (pt) |
LT (1) | LT3092227T (pt) |
MA (1) | MA39172B1 (pt) |
MX (1) | MX2016009052A (pt) |
MY (1) | MY190835A (pt) |
PE (1) | PE20161021A1 (pt) |
PH (1) | PH12016501355A1 (pt) |
PL (1) | PL3092227T3 (pt) |
PT (1) | PT3092227T (pt) |
RS (1) | RS57586B1 (pt) |
SA (1) | SA516371448B1 (pt) |
SG (1) | SG11201604916YA (pt) |
SI (1) | SI3092227T1 (pt) |
UA (1) | UA117165C2 (pt) |
WO (1) | WO2015104653A1 (pt) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018522871A (ja) * | 2015-07-02 | 2018-08-16 | オリオン コーポレーション | ブロモドメイン阻害剤としての二環式複素環誘導体 |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2970282B1 (en) | 2013-03-15 | 2019-08-21 | Incyte Holdings Corporation | Tricyclic heterocycles as bet protein inhibitors |
US9309246B2 (en) | 2013-12-19 | 2016-04-12 | Incyte Corporation | Tricyclic heterocycles as BET protein inhibitors |
MY180775A (en) | 2014-04-23 | 2020-12-09 | Incyte Corp | 1h-pyrrolo[2,3-c]pyridin-7(6h)-ones and pyrazolo[3,4-c]pyridin-7(6h)-ones as inhibitors of bet proteins |
JP6599979B2 (ja) | 2014-09-15 | 2019-10-30 | インサイト・コーポレイション | Betタンパク質阻害剤として用いるための三環式複素環化合物 |
MX2018001751A (es) | 2015-08-11 | 2018-08-01 | Neomed Inst | Dihidroquinolinonas aril-sustituidas, su preparacion y su uso como farmaceuticos. |
US10836742B2 (en) | 2015-08-11 | 2020-11-17 | Neomed Institute | N-substituted bicyclic lactams, their preparation and their use as pharmaceuticals |
AU2016305515A1 (en) | 2015-08-12 | 2018-03-08 | Neomed Institute | Substituted benzimidazoles, their preparation and their use as pharmaceuticals |
US10501459B2 (en) | 2015-10-21 | 2019-12-10 | Neomed Institute | Substituted imidazo[1,2-a]pyridines as bromodomain inhibitors |
TW201722966A (zh) | 2015-10-29 | 2017-07-01 | 英塞特公司 | Bet蛋白質抑制劑之非晶固體形式 |
CN105198871A (zh) * | 2015-11-06 | 2015-12-30 | 中国药科大学 | 一类喹喔啉酮类化合物及其制备方法和用途 |
US10519151B2 (en) | 2016-01-28 | 2019-12-31 | Neomed Institute | Substituted [1,2,4]triazolo[4,3-A]pyridines, their preparation and their use as pharmaceuticals |
JP2019513804A (ja) | 2016-04-18 | 2019-05-30 | セルジーン クオンティセル リサーチ,インク. | 治療用化合物 |
DE102017005089A1 (de) | 2016-05-30 | 2017-11-30 | Bayer Pharma Aktiengesellschaft | Substitulerte 3,4-Dihydrochinoxalin-2(1H)-one |
EP4234554A3 (en) | 2016-06-20 | 2023-12-27 | Incyte Corporation | Crystalline solid forms of a bet inhibitor |
WO2018114662A1 (de) | 2016-12-22 | 2018-06-28 | Bayer Cropscience Aktiengesellschaft | Substituierte 1,2,4-thiadiazolylpyrrolone und 1,2,4-thiadiazolylhydantoine sowie deren salze und ihre verwendung als herbizide wirkstoffe |
WO2018114663A1 (de) | 2016-12-22 | 2018-06-28 | Bayer Cropscience Aktiengesellschaft | Substituierte azolylpyrrolone und azolylhydantoine sowie deren salze und ihre verwendung als herbizide wirkstoffe |
CN108570038B (zh) * | 2017-03-08 | 2021-09-28 | 中国科学院上海药物研究所 | 二氢喹喔啉类溴结构域识别蛋白抑制剂及制备方法和用途 |
US10617680B2 (en) | 2017-04-18 | 2020-04-14 | Celgene Quanticel Research, Inc. | Therapeutic compounds |
CN110092782B (zh) * | 2018-01-30 | 2022-10-21 | 中国科学院广州生物医药与健康研究院 | 一种苯并六元氮杂环化合物及其制备方法和应用 |
CN110960528A (zh) * | 2018-09-30 | 2020-04-07 | 四川大学 | Ar和bet双重抑制剂及其用途 |
AU2019372121A1 (en) | 2018-10-30 | 2021-05-27 | Nuvation Bio Inc. | Heterocyclic compounds as BET inhibitors |
CA3132934A1 (en) | 2019-04-11 | 2020-10-15 | Eila Luukkonen | Crystalline form of a bet-inhibitor and manufacture thereof |
AU2020299592A1 (en) | 2019-07-02 | 2022-02-17 | Nuvation Bio Inc. | Heterocyclic compounds as BET inhibitors |
US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
KR102600176B1 (ko) * | 2021-10-18 | 2023-11-10 | 주식회사 사피엔스바이오 | 신규한 화합물 및 이를 포함하는 약학적 조성물 |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10259176A (ja) * | 1997-03-17 | 1998-09-29 | Japan Tobacco Inc | 血管新生阻害作用を有する新規アミド誘導体及びその用途 |
MX2007003735A (es) * | 2004-09-28 | 2007-04-23 | Otsuka Pharma Co Ltd | Compuesto de carboestirilo. |
MY144974A (en) * | 2005-06-14 | 2011-11-30 | Eisai R&D Man Co Ltd | 1,2-di(cyclic) substituted benzene derivatives |
JP5191155B2 (ja) * | 2006-03-27 | 2013-04-24 | 大塚製薬株式会社 | カルボスチリル化合物からなる医薬 |
JP2008156311A (ja) | 2006-12-26 | 2008-07-10 | Institute Of Physical & Chemical Research | Brd2ブロモドメイン結合剤 |
TW200918058A (en) * | 2007-08-31 | 2009-05-01 | Organon Nv | TSH receptor antagonizing tetrahydroquinoline compounds |
EP2203447B1 (en) * | 2007-09-21 | 2012-02-29 | Janssen Pharmaceutica, N.V. | Inhibitors of the interaction between mdm2 and p53 |
WO2009084693A1 (ja) | 2007-12-28 | 2009-07-09 | Mitsubishi Tanabe Pharma Corporation | 抗癌剤 |
WO2010074807A1 (en) | 2008-10-30 | 2010-07-01 | Gilead Palo Alto, Inc. | 3, 4-dihydroquinolin-2 ( 1h ) -one derivatives as sodium channel modulators |
GB0919434D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
GB0919423D0 (en) | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
JP6063870B2 (ja) * | 2010-11-08 | 2017-01-18 | ライセラ・コーポレイション | RORγ活性の阻害用のN−スルホニル化テトラヒドロキノリンおよび関連二環化合物および病気の治療 |
GB201106750D0 (en) * | 2011-04-21 | 2011-06-01 | Glaxosmithkline Llc | Novel compounds |
GB201107325D0 (en) * | 2011-05-04 | 2011-06-15 | Glaxosmithkline Llc | Novel compounds |
WO2013027168A1 (en) * | 2011-08-22 | 2013-02-28 | Pfizer Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
EP2844247A4 (en) * | 2012-04-20 | 2015-11-25 | Anderson Gaweco | ROR MODULATORS AND ITS USES |
US9447069B2 (en) * | 2012-04-30 | 2016-09-20 | Innov17 Llc | ROR modulators and their uses |
EP2968360B1 (en) * | 2013-03-14 | 2021-01-20 | ConverGene LLC | Quinolinone derivatives for the inhibition of bromodomain-containing proteins |
US9199988B2 (en) | 2013-03-27 | 2015-12-01 | Boehringer Ingelheim International Gmbh | Dihydroquinazolinone analogues |
-
2015
- 2015-01-06 BR BR112016015311-1A patent/BR112016015311B1/pt not_active IP Right Cessation
- 2015-01-06 MA MA39172A patent/MA39172B1/fr unknown
- 2015-01-06 AU AU2015205339A patent/AU2015205339B2/en active Active
- 2015-01-06 KR KR1020167021643A patent/KR102394518B1/ko active IP Right Grant
- 2015-01-06 MX MX2016009052A patent/MX2016009052A/es unknown
- 2015-01-06 CA CA2934788A patent/CA2934788C/en active Active
- 2015-01-06 LT LTEP15703314.3T patent/LT3092227T/lt unknown
- 2015-01-06 SG SG11201604916YA patent/SG11201604916YA/en unknown
- 2015-01-06 PE PE2016001002A patent/PE20161021A1/es active IP Right Grant
- 2015-01-06 DK DK15703314.3T patent/DK3092227T3/en active
- 2015-01-06 JP JP2016545312A patent/JP6480944B2/ja active Active
- 2015-01-06 HU HUE15703314A patent/HUE041546T2/hu unknown
- 2015-01-06 UA UAA201608674A patent/UA117165C2/uk unknown
- 2015-01-06 WO PCT/IB2015/050090 patent/WO2015104653A1/en active Application Filing
- 2015-01-06 CN CN201580004048.2A patent/CN106061966B/zh active Active
- 2015-01-06 SI SI201530357T patent/SI3092227T1/sl unknown
- 2015-01-06 EP EP15703314.3A patent/EP3092227B1/en active Active
- 2015-01-06 US US15/110,361 patent/US10077259B2/en active Active
- 2015-01-06 ES ES15703314.3T patent/ES2687497T3/es active Active
- 2015-01-06 RS RS20180847A patent/RS57586B1/sr unknown
- 2015-01-06 MY MYPI2016001265A patent/MY190835A/en unknown
- 2015-01-06 EA EA201691404A patent/EA029224B1/ru not_active IP Right Cessation
- 2015-01-06 PL PL15703314T patent/PL3092227T3/pl unknown
- 2015-01-06 PT PT15703314T patent/PT3092227T/pt unknown
-
2016
- 2016-06-09 IL IL246140A patent/IL246140B/en active IP Right Grant
- 2016-07-03 SA SA516371448A patent/SA516371448B1/ar unknown
- 2016-07-07 CL CL2016001737A patent/CL2016001737A1/es unknown
- 2016-07-08 PH PH12016501355A patent/PH12016501355A1/en unknown
-
2018
- 2018-08-01 US US16/051,913 patent/US10590118B2/en active Active
- 2018-09-18 CY CY20181100961T patent/CY1122046T1/el unknown
- 2018-10-11 HR HRP20181650TT patent/HRP20181650T1/hr unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018522871A (ja) * | 2015-07-02 | 2018-08-16 | オリオン コーポレーション | ブロモドメイン阻害剤としての二環式複素環誘導体 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6480944B2 (ja) | ブロモドメイン阻害剤としての二環式複素環誘導体 | |
US10807982B2 (en) | Bromodomain inhibitors | |
EP3057586A1 (en) | Bromodomain inhibitors | |
WO2014128655A1 (en) | Substituted imidazo[4,5-c]quinoline derivatives as bromodomain inhibitors | |
JP2006528193A (ja) | C−fmsキナーゼの阻害剤としてのキノリノン誘導体 | |
EP1807413A1 (en) | Anthranilamide pyridinureas as vegf receptor kinase inhibitors | |
JP2018527293A (ja) | ブロモドメイン阻害剤としてのスピロ[シクロブタン−1,3’−インドリン]−2’−オン誘導体 | |
WO2017007694A1 (en) | 6-amino-quinoline-3-carbonitrils as cot modulators | |
JP2018522871A (ja) | ブロモドメイン阻害剤としての二環式複素環誘導体 | |
NZ721993B2 (en) | Bicyclic heterocyclic derivatives as bromodomain inhibitors | |
WO2019120256A1 (zh) | 五元杂芳环衍生物、其药物组合物及应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20171208 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180919 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180925 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181206 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190205 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190208 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6480944 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |